Pediatric pulmonary vascular diseases (PVD), including pediatric pulmonary hypertension (PH), are high morbidity and mortality conditions, yet treatment options are limited. Despite new drug therapies, survival of patients with severe PH remains poor. Although most clinical studies have emphasized disease in adults, pediatric PVD can be devastating, contributing substantially to poor outcomes in newborns, infants and children that are strikingly different from those encountered in adults. Unfortunately, very few studies have addressed the safety and efficacy of PVD therapies in children. Current approaches to PVD are limited by small numbers of patients with PH and the association of PH with a variety of pediatric disorders and subspecialties at any individual center; by few established, multidisciplinary programs in pediatric PH; and by limited interactions among existing PVD programs. Multi-center investigations are necessary for sufficiently powered interventional studies, but study designs have been restricted by lack of knowledge as to disease phenotypes, clinical course, outcomes, and age-appropriate endpoints. Our objective, therefore, is the establishment and operation of a Bioinformatics Clinical Coordinating Center (BCCC) for advancing the understanding and treatment of PVD in children, comprised of national leaders in pediatric pulmonary and cardiac medicine, informatics, and biostatistics as well as registry-based and electronic health records (EHR) clinical research. We leverage and extend the existing Pediatric Pulmonary Hypertension Network (PPHnet) for large-scale registry and EHR-based research, using a well tested and widely adopted open-source data warehouse technology infrastructure (i2b2/SHRINE), developed through the NIH National Centers for Biocomputing and Clinical and Translational Science Award (CTSA) Programs. The goal of this proposal is three-fold: (1) establish a sustainable, open source, reusable registry infrastructure across 8 PPHnet sites to capture multi-sourced EHR, traditional prospective patient-based data, and patient reported outcomes (PROs) across a large, prospective, pediatric pulmonary hypertension (PH) observational cohort; (2) enroll >500 registry subjects and capture data on >750 EHR subjects across 8 PPHnet sites, linking EHR with registry data at 3 sites; (3) address three classes of unanswered questions crucial for the characterization and management of PH, comparing the information value of registry vs. EHR vs. fused data across registry/EHR/PROs, in the domains of spectrum of PH comorbidities, PH indicators and endpoints of morbidity and mortality, and response to therapies in PH.